scholarly journals Inhibition of 11β-Hydroxysteroid Dehydrogenase Type 1 Activity in Vivo Limits Glucocorticoid Exposure to Human Adipose Tissue and Decreases Lipolysis

2007 ◽  
Vol 92 (3) ◽  
pp. 857-864 ◽  
Author(s):  
Jeremy W. Tomlinson ◽  
Mark Sherlock ◽  
Beverley Hughes ◽  
Susan V. Hughes ◽  
Fiona Kilvington ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Single Dose ◽  
Interstitial Fluid ◽  
Human Adipose Tissue ◽  
Serum Cortisol ◽  
Hydroxysteroid Dehydrogenase ◽  
Continuous Treatment ◽  
Gas Chromatography Mass Spectrometry ◽  
Glycerol Release

Abstract Context: The pathophysiological importance of glucocorticoids (GCs) is exemplified by patients with Cushing’s syndrome who develop hypertension, obesity, and insulin resistance. At a cellular level, availability of GCs to the glucocorticoid and mineralocorticoid receptors is controlled by the isoforms of 11β-hydroxysteroid dehydrogenase (11β-HSD). In liver and adipose tissue, 11β-HSD1 converts endogenous, inactive cortisone to active cortisol but also catalyzes the bioactivation of the synthetic prednisone to prednisolone. Objective: The objective of the study was to compare markers of 11β-HSD1 activity and demonstrate that inhibition of 11β-HSD1 activity limits glucocorticoid availability to adipose tissue. Design and Setting: This was a clinical study. Patients: Seven healthy male volunteers participated in the study. Intervention: Intervention included carbenoxolone (CBX) single dose (100 mg) and 72 hr of continuous treatment (300 mg/d). Main Outcome Measures: Inhibition of 11β-HSD1 was monitored using five different mechanistic biomarkers (serum cortisol and prednisolone generation, urinary corticosteroid metabolite analysis by gas chromatography/mass spectrometry, and adipose tissue microdialysis examining cortisol generation and glucocorticoid-mediated glycerol release). Results: Each biomarker demonstrated reduced 11β-HSD1 activity after CBX administration. After both a single dose and 72 hr of treatment with CBX, cortisol and prednisolone generation decreased as did the urinary tetrahydrocortisol+5α-tetrahydrocortisol to tetrahydrocortisone ratio. Using adipose tissue microdialysis, we observed decreased interstitial fluid cortisol availability with CBX treatment. Furthermore, a functional consequence of 11β-HSD1 inhibition was observed, namely decreased prednisone-induced glycerol release into adipose tissue interstitial fluid indicative of inhibition of GC-mediated lipolysis. Conclusion: CBX is able to inhibit rapidly the generation of active GC in human adipose tissue. Importantly, limiting GC availability in vivo has functional consequences including decreased glycerol release.

scholarly journals Long-Term Severe In Vitro Hypoxia Exposure Enhances the Vascularization Potential of Human Adipose Tissue-Derived Stromal Vascular Fraction Cell Engineered Tissues

2021 ◽  
Vol 22 (15) ◽  
pp. 7920
Author(s):  
Myroslava Mytsyk ◽  
Giulia Cerino ◽  
Gregory Reid ◽  
Laia Gili Sole ◽  
Friedrich S. Eckstein ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Therapeutic Potential ◽  
Stromal Vascular Fraction ◽  
Human Adipose Tissue ◽  
Bioreactor Culture ◽  
Proliferating Cells ◽  
Angiogenic Potential ◽  
Engineered Tissues

The therapeutic potential of mesenchymal stromal/stem cells (MSC) for treating cardiac ischemia strongly depends on their paracrine-mediated effects and their engraftment capacity in a hostile environment such as the infarcted myocardium. Adipose tissue-derived stromal vascular fraction (SVF) cells are a mixed population composed mainly of MSC and vascular cells, well known for their high angiogenic potential. A previous study showed that the angiogenic potential of SVF cells was further increased following their in vitro organization in an engineered tissue (patch) after perfusion-based bioreactor culture. This study aimed to investigate the possible changes in the cellular SVF composition, in vivo angiogenic potential, as well as engraftment capability upon in vitro culture in harsh hypoxia conditions. This mimics the possible delayed vascularization of the patch upon implantation in a low perfused myocardium. To this purpose, human SVF cells were seeded on a collagen sponge, cultured for 5 days in a perfusion-based bioreactor under normoxia or hypoxia (21% and <1% of oxygen tension, respectively) and subcutaneously implanted in nude rats for 3 and 28 days. Compared to ambient condition culture, hypoxic tension did not alter the SVF composition in vitro, showing similar numbers of MSC as well as endothelial and mural cells. Nevertheless, in vitro hypoxic culture significantly increased the release of vascular endothelial growth factor (p < 0.001) and the number of proliferating cells (p < 0.00001). Moreover, compared to ambient oxygen culture, exposure to hypoxia significantly enhanced the vessel length density in the engineered tissues following 28 days of implantation. The number of human cells and human proliferating cells in hypoxia-cultured constructs was also significantly increased after 3 and 28 days in vivo, compared to normoxia. These findings show that a possible in vivo delay in oxygen supply might not impair the vascularization potential of SVF- patches, which qualifies them for evaluation in a myocardial ischemia model.

Hepatocyte differentiation of mesenchymal stem cells from human adipose tissue in vitro promotes hepatic integration in vivo

Gut ◽  
2008 ◽  
Vol 58 (4) ◽  
pp. 570-581 ◽  
Author(s):  
H Aurich ◽  
M Sgodda ◽  
P Kaltwasser ◽  
M Vetter ◽  
A Weise ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Human Adipose Tissue ◽  
Hepatocyte Differentiation ◽  
Adipose Tissue In Vitro

scholarly journals Human Adipose-Derived Stromal/Stem Cell Culture and Analysis Methods for Adipose Tissue Modeling In Vitro: A Systematic Review

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1378
Author(s):  
Peyton Gibler ◽  
Jeffrey Gimble ◽  
Katie Hamel ◽  
Emma Rogers ◽  
Michael Henderson ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adipose Tissue ◽  
Drug Discovery ◽  
3D Culture ◽  
Human Adipose Tissue ◽  
Culture Methods ◽  
Adipose Tissue Engineering ◽  
The Impact

Human adipose-derived stromal/stem cells (hASC) are widely used for in vitro modeling of physiologically relevant human adipose tissue. These models are useful for the development of tissue constructs for soft tissue regeneration and 3-dimensional (3D) microphysiological systems (MPS) for drug discovery. In this systematic review, we report on the current state of hASC culture and assessment methods for adipose tissue engineering using 3D MPS. Our search efforts resulted in the identification of 184 independent records, of which 27 were determined to be most relevant to the goals of the present review. Our results demonstrate a lack of consensus on methods for hASC culture and assessment for the production of physiologically relevant in vitro models of human adipose tissue. Few studies have assessed the impact of different 3D culture conditions on hASC adipogenesis. Additionally, there has been a limited use of assays for characterizing the functionality of adipose tissue in vitro. Results from this study suggest the need for more standardized culture methods and further analysis on in vitro tissue functionality. These will be necessary to validate the utility of 3D MPS as an in vitro model to reduce, refine, and replace in vivo experiments in the drug discovery regulatory process.

scholarly journals In Vitro and in Vivo Calcitonin I Gene Expression in Parenchymal Cells: A Novel Product of Human Adipose Tissue

Endocrinology ◽  
2003 ◽  
Vol 144 (12) ◽  
pp. 5578-5584 ◽  
Author(s):  
Philippe Linscheid ◽  
Dalma Seboek ◽  
Eric S. Nylen ◽  
Igor Langer ◽  
Mirjam Schlatter ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Human Adipose Tissue ◽  
Parenchymal Cells ◽  
I Gene

Enhanced triglyceride clearance with intraperitoneal human acylation stimulating protein in C57BL/6 mice

1999 ◽  
Vol 277 (3) ◽  
pp. E474-E480 ◽  
Author(s):  
Ian Murray ◽  
Allan D. Sniderman ◽  
Katherine Cianflone
Keyword(s):  
Adipose Tissue ◽  
Area Under The Curve ◽  
Human Adipose Tissue ◽  
Plasma Triglyceride ◽  
Complement C3 ◽  
Postprandial Period ◽  
Postprandial Triglyceride ◽  
Acylation Stimulating Protein

Acylation stimulating protein (ASP), a novel adipocyte-derived autocrine protein, stimulates triglyceride synthesis and glucose transport in vitro in human and murine adipocytes. In vitro, chylomicrons increase ASP and precursor complement C3 production in adipocytes. Furthermore, in vivo, ASP production from human adipose tissue correlates positively with triglyceride clearance postprandially. The aim of the present study was to determine if intraperitoneally injected ASP accelerated triglyceride clearance in vivo after a fat load in C57Bl/6 mice. ASP increased the triglyceride clearance with a reduction of the triglyceride area under the curve over 6 h (AUC0–6) from 102.6 ± 30.0 to 61.0 ± 14.5 mg ⋅ dl−1 ⋅ h−1( P < 0.05), especially in the latter postprandial period (AUC3–6; 56.2 ± 18.0 vs. 24.9 ± 8.9 mg ⋅ dl−1 ⋅ h−1, P < 0.025). ASP also reduced plasma glucose both in the mice with accelerated plasma triglyceride clearance and in those with relatively delayed triglyceride clearance ( P < 0.025). Therefore, ASP alters postprandial triglyceride and glucose metabolism.

Determination of Halogenated Contaminants in Human Adipose Tissue

1986 ◽  
Vol 69 (3) ◽  
pp. 451-458
Author(s):  
Guy L Lebel ◽  
David T Williams
Keyword(s):  
Gas Chromatography ◽  
Adipose Tissue ◽  
Methylene Chloride ◽  
Gel Permeation Chromatography ◽  
Human Adipose Tissue ◽  
Gas Chromatography Mass Spectrometry ◽  
Selected Ion Monitoring ◽  
Fat Extraction ◽  
Capillary Column Gas Chromatography

Abstract &lt;A method has been developed for determination of organochlorine contaminants in human adipose tissue. After fat extraction from the tissue with acetone-hexane (15 + 85, v/v), organochlorines were fractionated from fat by gel permeation chromatography with methylene chloride-cyclohexane (1 + 1, v/v) as solvent. After Florisil column cleanup, the GPC extract was analyzed by capillary column gas chromatography using 2 columns of different polarity. Compound identity was confirmed by gas chromatography-mass spectrometry using selected ion monitoring. Recoveries for fortification levels of 10-500 ng/g were greater than 80 % except for trichlorobenzene and hexachlorobutadiene (ca 60%).

Importance of the Cyclic AMP Concentration for the Rate of Lipolysis in Human Adipose Tissue

1980 ◽  
Vol 59 (3) ◽  
pp. 199-201 ◽  
Author(s):  
P. Arner ◽  
J. Östman
Keyword(s):  
Adipose Tissue ◽  
Cyclic Amp ◽  
Subcutaneous Adipose Tissue ◽  
Human Adipose Tissue ◽  
Strong Positive Correlation ◽  
Glycerol Release ◽  
Two Parameters ◽  
Subcutaneous Adipose ◽  
The Relationship ◽  
Release Of Glycerol

1. The activation of lipolysis on incubation of human subcutaneous adipose tissue was examined in terms of the relationship between the release of glycerol and the concentration of tissue cyclic AMP. 2. A strong positive correlation was obtained between the maximum concentration of cyclic AMP and the rate of glycerol release in the presence of noradrenaline (r = 0.9), whereas, in the basal state, these two parameters were only weakly correlated (r = 0.45). 3. It appears that the noradrenaline-induced rate of lipolysis depends upon the maximal concentration of cyclic AMP that is present in human adipose tissue.

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